Aspirin and other non-steroidal anti-inflammatory drugs are widely used to treat pain and inflammation, and at low doses, aspirin is also increasingly being used for cardiovascular prophylaxis. However, these drugs have substantial gastrointestinal toxicity and a significant number of patients develop peptic ulcers and GI bleeding. Although infection with Helicobacter pylori is another major risk factor for ulcers, the relationships between aspirin and H. pylori in the development of ulcers remain highly controversial. It is unclear, for example, whether there is an addictive or synergistic interaction between these factors in conferring ulcer risk such that aspirin interacts with H. pylori to increase ulcer complications. Aspirin impairs mucosal protective mechanisms by decreasing prostaglandin production, whereas H. pylori promotes mucosal injury through cytokines and inflammation to form ulcers. Past studies have provided conflicting data on the ulcer risks associated with both factors but they have been limited by recall bias of aspirin use, selection bias, and small sample sizes with short follow-up. The primary goals of the proposed research are to determine the risk of peptic ulcers associated with the joint effects of low dose aspirin and H. pylori infection, the ulcer risk associated with low dose aspirin and a specific virulent strain of H. pylori, known as cagA+ H. pylori, and the risk of GI bleeding associated with low dose aspirin and H. pylori (especially cagA+ H. pylori strains) as compared to those without infection. We will have 80% power to detect a difference of 1.56 in the odds ratio, when comparing the association of aspirin use and ulcer formation in H. pylori positive and negative subjects. As the US population grows older, the chronic use of aspirin for cardiovascular prophylaxis and the subsequent development of ulcers are likely to increase, involving health care costs. The proposed study will provide important information to make an informed decision about aspirin related GI complications and whether H. pylori infected patients are at risk for ulcers and GI bleeding while on aspirin. These results may help identify high-risk patients and lead to strategies that will reduce ulcer complications among aspirin users.